A Signature Predicts Prognosis of Patients with Adrenocortical Carcinoma

Jianyu Zhao China-Japan Union Hospital of Jilin University Bo Liu China-Japan Union Hospital of Jilin University Xiaoping Li (  [email protected] ) Jilin University First Hospital https://orcid.org/0000-0001-6463-7922

Research

Keywords: Adrenocortical carcinoma, TCGA, GEO, transcription factor, prognosis

Posted Date: February 9th, 2021

DOI: https://doi.org/10.21203/rs.3.rs-178087/v1

License:   This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License

Page 1/17 Abstract

Background: Adrenocortical carcinoma (ACC) is a rare endocrine cancer that manifests as abdominal masses and excessive steroid hormone levels. Transcription factors (TFs) deregulation is found to be involved in adrenocortical tumorigenesis and cancer progression. This study aimed to construct a TF-based prognostic signature for prediction of survival of ACC patients.

Methods: The expression profle for ACC patients were downloaded from TCGA and GEO datasets. The univariate Cox analysis was applied to identify survival-related TFs and the LASSO Cox regression was conducted to construct the TF signature. The multivariate analysis was used to reveal the independent prognostic factors.

Results: We identifed a 13-TF prognostic signature comprised of CREB3L3, NR0B1, CENPA, FOXM1, , MYBL2, HOXC11, ZIC2, ZNF282, DNMT1, TCF3, ELK4, and KLF6 using the univariate Cox analysis and LASSO Cox regression. The risk score based on the TF-signature could classify patients into low- and high-risk group. Kaplan- Meier analyses showed that patients in the high-risk group had signifcantly shorter overall survival compared to the low-risk patients. ROC curves showed that the prognostic signature predicted the overall survival of ACC patients with good sensitivity and specifcity. Furthermore, the TF-risk score was an independent prognostic factor.

Conclusion: Taken together, we identifed a 13-TF prognostic marker to predict overall survival in ACC patients.

1 Background

Adrenocortical carcinoma (ACC) is a rare endocrine cancer with an annual incidence of 0.7-2.0 cases per million 1,2. It usually affects adults aged around 40–50 years and children younger than 10 years 3,4. Clinical manifestations of ACC include abdominal masses and elevated steroid hormones, and result in overall poor outcomes with fve-year survival ranging from 32–45% 5. Therefore, it is essential to identify prognostic markers of ACC in order to screen for patients at high risk.

Transcription factors (TFs) are regulatory that bind to the promoter sequences of and decrease or increase their transcription 6, and thus control cell differentiation 7, proliferation 8 and death 9. Not surprisingly, the genes encoding TFs are often aberrantly expressed in human cancers and developmental disorders 10. For instance, and c- mutations are correlated with poor clinical outcomes in cancer patients 11–14. In addition, overexpression of the forkhead box transcription factor FoxP3 is an independent prognostic factor for the overall survival of patients with ovarian cancer 15, while is related to adverse prognosis in patients with non-small cell lung carcinomas 16. In recent years, TF-related signatures, such as that of p53 17 and STAT3 18, have been identifed in several cancers. Snail is overexpressed in numerous ACC patients and associated with decreased survival 19. In addition, TGF-β pathway components including GATA-6 and SF-1 are also correlated with poor outcomes in ACC patients 20.